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Exogenous secretin and cholecystokinin (CCK) have been shown to stimulate the growth of the exocrine pancreas. To conclude that a hormone produces an effect under normal physiological conditions, one must demonstrate that the endogenous hormone also produces the action in question. To release endogenous secretin 0.01 N HCl was continuously infused into the duodenums of eight rats for 5 days. Sixteen animals were prepared with catheters inserted 1 cm below the pylorus. The other eight animals were infused with PO4 buffer, pH 7.5. The infusion rate for both groups was 2 ml/h. Animals were killed at the end of 5 days, and the oxyntic gland mucosa and pancreas were examined. Pancreatic weights, DNA synthesis, DNa, RNA, and protein content were significantly increased in rats receiving acid. An identical experiment was set up to release endogenous CCK. In this experiment eight rats received a solution containing 50 mM phenylalanine and 50 mM tryptophan. The controls received the caloric equivalent in glucose. At the end of 1 wk the pancreases of the rats infused with amino acids averaged 405 (P < 0.001) heavier than the controls. Similar increases occurred in DNA, RNA, and protein content. These studies suggest that endogenous secretin and CCK can be released in amounts sufficient to stimulate growth.

The relative efficacy of exogenous fat or glucose in preserving lean body mass in surgical patients is controversial. In this study, peripheral intravenously administered amino acids with either lipid or dextrose were given to well nourished patients undergoing elective total cystectomy and ileal diversion. Patients were well matched for age, sex, nutritional status and degree of operative stress. Twenty-eight patients received 1.2 grams per kilogram per day of amino acids plus either dextrose (440 kilocalories per day) (17 patients) or 10 per cent fat emulsion (550 kilocalories per day) (11 patients) for three days preoperatively and seven days postoperatively. No significant differences between the groups were noted in mean nitrogen balances during the preoperative and postoperative periods or in the mean cumulative adjusted (for change in blood urea nitrogen and body weight) nitrogen balances for the total study time. Mean nitrogen excretion per 100 nonprotein calories infused was also similar. Changes in mean body weight, blood urea nitrogen, serum glucose and serum albumin were similar in the two groups. No deaths or major infectious complications occurred in either group. In well nourished patients matched for age, sex, nutritional status and degree of operative stress, the addition of either hypocaloric fat or dextrose to intravenously infused amino acid solutions resulted in an equivalent metabolic and clinical outcome.

Oral and intravenous high calorie-amino acid nutritional therapy postoperatively resulted in significant weight gain, improved colonic wound healing and maintenance of normal intravascular albumin levels. Provision of caloric needs without amino acids minimized weight loss postoperatively. However, infusion of hypertonic dextrose solutions resulted in severe generalized hepatic fatty infiltration and marked hypoalbuminemia. Protein and calorie deprivation by administration of 5% dextrose and water resulted in the greatest postoperative weight loss, reduced intravascular albumin levels and decreased colonic anastomotic strength. Comparison of oral and intravenous diet administration demonstrated that hypertonic dextrose infusion was markedly deleterious to hepatic morphology and serum protein metabolism in normal rats. Further clinical investigation appears indicated in previously well-nourished patients undergoing extensive surgery who will not be able to ingest adequate nutrients in the postoperative period.

The incidence and severity of peripheral vein phlebitis was evaluated in patients receiving infusions of amino acids alone (1.4 g/kg/day) (group I), amino acids (1.4 g/kg/day) plus 5% dextrose (group II) and 5% dextrose alone (Group III). Ninety-three patients with carcinoma of the bladder were randomized to receive one of three peripheral parenteral nutrition solutions which were infused predominantly via scalp-vein needles. Peripheral parenteral nutrition solutions contained sodium and potassium chloride as necessary to maintain normal serum electrolyte levels. The osmolality of each solution was calculated. Peripheral intravenous sites were evaluated every 8 hr and at the time of each intravenous site change. The incidence of infiltration, phlebitis and its' severity was recorded and graded zero (no complications) to 4 (severe complications). An intravenous cannula was discontinued if infiltration or a grade 2 or greater phlebitis occurred. The mean osmolality of the solutions were (group I) 450 to 500 mosm/liter, (group II) 713 to 763 mosm/liter and (group III) 369 mosm/liter. The mean duration of infusion was 9.0 + 0.4, 9.1 + 0.4, and 8.7 + 0.5 days, respectively, and the mean number of intravenous site changes were 6.1 + 0.3, 5.8 + 0.3, and 5.6 + 0.3, respectively. Infiltration preceded 57, 56, and 58% of all intravenous site changes and the incidence and severity of peripheral vein phlebitis was similar for all three groups. Sixty patients who received their infusions via plastic indwelling catheters for a mean duration of 2.6 + 1.0, 2,3 + 1.0, and 2.8 + 1.0 days had an 86, 71, and 76% incidence of grade two or greater phlebitis, respectively. There was no significant difference in the incidence of infiltration and phlebitis in patients receiving peripheral parenteral infusions of amino acids alone, amino acids plus dextrose, and 5% dextrose alone.

Urine ketone levels were measured in patients receiving peripheral amino acid solutions, and the results were correlated with changes in nitrogen balance. Thirty well-nourished patients who were to undergo cystectomy were placed on liquid, noncarbohydrate diets 3 days before operation, and no oral intake was allowed until 7 days after operation. Crystalline amino acid (1.3 to 1.5 gm/kg/day) solutions were infused continuously from 3 days before to 7 days after operation. Blood was obtained 3 days before and 3, 7, and 10 days after operation; 24-hour urine outputs were determined daily. Qualitative urine acetone levels were determined four times daily. During the infusion period, 14 (47%) patients developed ketonuria (group I); 16 patients did not (group II). The mean serum glucose levels ranged from 99 to 107 mg/dl in group I and from 108 to 113 mg/dl in group II (P less than 0.05). The mean serum transferrin level decreased after operation to 117 mg/dl in group I and 97 mg/dl in group II. The mean cumulative adjusted nitrogen balance was -24 +/- 8 gm in group I and -47 +/- 9 gm in group II (P less than 0.05). No patient developed sepsis. Qualitative testing of urinary ketones correlated with significant alterations in blood urea nitrogen, serum glucose, transferrin, and cumulative adjusted nitrogen balance. The bedside determination of urinary ketones may be useful in assessing a patient's adaptation to peripheral amino acid infusions.

Preliminary studies in 400 New Zealand albino rabbits produced a reliable animal model of nutrient-induced atherosclerosis that simulated that observed in humans. Atherosclerosis was then induced in an additional 1600 rabbits in sets of 40 animals each, maintaining plasma cholesterol concentrations between 1000 and 2000 mg/dL for 6-20 weeks. In each set, 10 control rabbits were killed to document baseline atherosclerosis, and the other 30 rabbits were assigned randomly to one of three groups of 10 rabbits. Groups of 10 rabbits were either continued on the atherogenic diet (group I), given standard laboratory rabbit pellets (group II), or infused continuously with specially formulated anticholesterol solutions via central venous catheters (group III) for 6 weeks. At autopsy, atherosclerotic lesions consistently involved 85-95% of the aorta in group I. In group II, atherosclerosis was comparable with the baseline control group with no regression. In group III, regression of atherosclerosis by 90-95% was consistently documented. Correlations between plasma amino acids and plasma cholesterol concentrations were established in four humans with severe atherosclerosis to maximize the cholesterol reduction capacity of the amino acid formulation. Infusion of the modified total parenteral nutrition solution induced prompt reduction in plasma cholesterol levels by 40-60% regardless of the initial level and was accompanied by evidence of regression of atherosclerosis after a 90-day infusion therapy period.